Genetic inactivation of adenosine A2A receptors attenuates acute traumatic brain injury in the mouse cortical impact model.
The inactivation of the A(2A) receptor (A(2A)R) has been shown to neuroprotect against brain injury in several animal models of neurological disorders including stroke and Parkinson's disease. However, despite marked elevation of adenosine level, the role of the A(2A) in traumatic brain injury (TBI) remains unclear. In the present study, we investigated the effects of genetic inactivation of A(2A)Rs in the acute stage. The A(2A)R knock-out (KO) mice and their wild-type (WT) littermates were subjected to cortical impact injury by a dropping weight. The control group was only craniotomized without TBI. At 24 h post-TBI, the neurological deficit scores of the KO mice were significantly lower than that of WT littermates. Consistent with the behavioral changes, the brain water contents as well as histological changes and the TUNEL-positive cells of the injured cortex of the KO mice were significantly lower than that of WT littermates. Furthermore, the glutamate level in the cerebral spinal fluid (CSF) of the KO mice was also significantly lower than that of WT littermates. In addition, we found that at 12 h post-TBI the mRNA and protein levels of TNF-alpha and IL-1beta were higher in the KO mice than that in the WT littermates. However, at 24 h post-TBI, the level of TNF-alpha and IL-1beta continually increased in the WT mice but largely declined in the KO mice. These results suggest that the genetic inactivation of A(2A)R protects against TBI, which is mainly associated with the suppression of glutamate level.
Li
Wei
W
The Molecular Biology Center, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
Dai
Shuangshuang
S
An
Jianhong
J
Xiong
Renping
R
Li
Ping
P
Chen
Xingyun
X
Zhao
Yan
Y
Liu
Ping
P
Wang
Hua
H
Zhu
Peifang
P
Chen
Jiangfan
J
Zhou
Yuanguo
Y
D000704:Analysis of Variance; D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000235:genetics; D001930:Brain Injuries / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death; D002540:Cerebral Cortex / Q000473:pathology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007839:Functional Laterality; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000134:cerebrospinal fluid; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009422:Nervous System Diseases / Q000209:etiology / Q000235:genetics; D043705:Receptor, Adenosine A2A / Q000172:deficiency* / Q000235:genetics; D018709:Statistics, Nonparametric
D016207:Cytokines; D043705:Receptor, Adenosine A2A; D018698:Glutamic Acid